RESUMO
OBJECTIVE: The present study compared three models of induction of osteoarthritis (OA) and rheumatoid arthritis (RA) in the temporomandibular joint (TMJ) of rats. DESIGN: The induction method was by injection of complete Freund's adjuvant (CFA) + type II bovine collagen (CII). Twenty-four adult male rats were divided into four groups (n = 6): G1: Sham, 50 µL of 0.9% sodium chloride at the base of the tail and in each TMJ; G2: OA, 50 µL CFA+CII in each TMJ; G3: RA+OA, 100 µL of CFA+CII at the base of the tail and 50 µL CFA+CII in each TMJ; G4: RA, 100 µL of CFA+CII at the base of the tail. All injections were repeated 5 days later. Twenty-three days after the first injection, the animals were sacrificed and the TMJs were submitted to histomorphometric analysis and measurement of cytokines. The Kruskal-Wallis and Dunn tests were used (alpha=0.05). RESULTS: The total thickness of the condylar cartilage increased in G2 in relation to the other groups, G3 and G4 reduced in relation to G1; and G2 and G4 reduced in relation to G2 and G3. The levels of IL-1ß, IL-6 and TNF-α increased in the three induction models compared to G1. The level of IL-10 increased in G2 compared to the other groups and reduced in G3 and G4 compared to G1. CONCLUSION: CFA+CII induced inflammation and degeneration compatible with RA (advanced chronic stage) when injected in the tail, and compatible with OA (acute stage or early disease) when injected only in the TMJ.
Assuntos
Artrite Reumatoide , Osteoartrite , Transtornos da Articulação Temporomandibular , Ratos , Masculino , Animais , Bovinos , Transtornos da Articulação Temporomandibular/induzido quimicamente , Articulação Temporomandibular , Osteoartrite/induzido quimicamente , Adjuvante de FreundRESUMO
BACKGROUND: P2X7 receptors are responsible for triggering inflammatory responses contributing to processes of pain in articular tissues. This study aimed to investigate whether the activation of the P2X7 receptor located in the temporomandibular joint (TMJ) tissues induces nociception through an inflammatory mechanisms and/or the activation of C-fibres (small-diameter primary afferents) of rats' TMJ. METHODS: The TMJ hypernociception induced by the activation of P2X7 receptor was assessed by measuring the behavioural nociceptive responses. After behavioural experiments, the animals were terminally anaesthetized and periarticular tissues were removed and homogenate for enzyme-linked immunosorbent assay, leukocyte infiltration and western blotting analysis. RESULTS: The nonselective P2X7 receptor agonist BzATP induced a dose-dependent TMJ nociception, which was blocked by the selective P2X7 receptor antagonist A-438079. The co-administration of the selective ß2-adrenoceptor antagonist (ICI-118,551) and the pre-treatment with cyclooxygenase inhibitor indomethacin or with the nonspecific selectin inhibitor Fucoidan significantly reduced BzATP-induced TMJ nociception. BzATP also induced an increase of pro-inflammatory cytokines TNFα, IL-1ß and CINC-1 levels, as well as leukocyte recruitment in TMJ tissue, effects that were reduced by A-438079. Moreover BzATP-induced TMJ nociception was inhibited in rats neonatal-treated with Capsaicin (depleting C-fibers). Finally, BzATP-induced an increase in TRPV1 expression in TMJ tissue. CONCLUSIONS: These findings suggest that P2X7 receptor activation in TMJ of rats induces nociceptive responses mediated by sympathomimetic amines, prostaglandins, leukocyte migration and increased levels of pro-inflammatory cytokines. Furthermore, the P2X7 receptor activation induces nociceptive responses dependent on the activation of the primary afferent nociceptors of rats' TMJ. SIGNIFICANCE: The activation of P2X7 receptors has an essential role in TMJ nociception and could be an interesting target to control the inflammatory pain in temporomandibular disorders.
Assuntos
Nociceptividade , Transtornos da Articulação Temporomandibular , Animais , Dor , Ratos , Ratos Wistar , Articulação Temporomandibular , Transtornos da Articulação Temporomandibular/induzido quimicamenteRESUMO
Painful conditions of the temporomandibular joint (TMJ) are challenging to manage and most attempts often result in unsatisfactory outcomes. In such context, nanocarrier systems, such as polymeric micelles, have been showing encouraging results in solving therapeutic limitations. Poloxamers are widely used, especially PL 407, because of their high biocompatibility and approval by the Food and Drug Administration (FDA) for clinical use. 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) has shown important antinociceptive and anti-inflammatory activity. The present study evaluated the efficacy and viability of the micellar system of PL-15dPGJ2 in a formalin-induced acute pain model in the temporomandibular joint of rats. The PL-15dPGJ2 was prepared and characterized. The animals were pretreated with an intra-articular injection of PL-15dPGJ2 followed by the formalin challenge. The nociceptive response was evaluated at different time-periods and the periarticular tissue and articular wash were collected for analysis. We found that intra-articular injection of PL-15d-PGJ2 produced pain relief at lower concentrations and in a sustained manner compared with free 15d-PGJ2. Moreover, a strong anti-inflammatory effect was observed with decreased levels of key pro-inflammatory cytokines and modulation of the leukocyte migration process. Our findings suggest that 15d-PGJ2 combined with a poloxamer micellar system provided clinical relevance in terms of bioavailability, long-lasting effect, and safe dosage. The formulation investigated herein is a promising micellar carrier system for managing pain conditions of the TMJ.
Assuntos
Anti-Inflamatórios/administração & dosagem , Artralgia/prevenção & controle , Portadores de Fármacos , Poloxâmero/química , Prostaglandina D2/análogos & derivados , Transtornos da Articulação Temporomandibular/prevenção & controle , Articulação Temporomandibular/efeitos dos fármacos , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacocinética , Artralgia/induzido quimicamente , Artralgia/metabolismo , Artralgia/fisiopatologia , Disponibilidade Biológica , Quimiotaxia de Leucócito/efeitos dos fármacos , Citocinas/metabolismo , Modelos Animais de Doenças , Composição de Medicamentos , Formaldeído , Mediadores da Inflamação/metabolismo , Injeções Intra-Articulares , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Masculino , Micelas , Prostaglandina D2/administração & dosagem , Prostaglandina D2/química , Prostaglandina D2/farmacocinética , Ratos Wistar , Articulação Temporomandibular/metabolismo , Articulação Temporomandibular/fisiopatologia , Transtornos da Articulação Temporomandibular/induzido quimicamente , Transtornos da Articulação Temporomandibular/metabolismo , Transtornos da Articulação Temporomandibular/fisiopatologia , Distribuição TecidualRESUMO
Inflammation of temporomandibular joint (TMJ) tissues are the most common cause of pain conditions associated with temporomandibular disorders (TMDs). After a tissue and/or neural damage, the inflammatory response is characterized by plasma extravasation and leukocytes infiltration in the TMJ tissues, which in turn, release inflammatory cytokines cascades responsible for inflammatory pain. Lectins are glycoproteins widely distributed in nature that may exhibit anti-inflammatory properties. This study demonstrated by molecular docking and MM/PBSA that the lectin from Dioclea violacea (DVL) interacts favorably with α-methyl-D-mannoside, N-acetyl-D-glucosamine, and core1-sialyl-Lewis X which are associated with leukocytes migration during an inflammatory response. Wistar rats pretreated with intravenously injection of DVL demonstrated a significant inhibition of plasma extravasation induced by carrageenan (a non-neurogenic inflammatory inductor) and mustard oil (a neurogenic inflammatory inductor) in the TMJ periarticular tissues (pâ¯<â¯0.05; ANOVA, Tukey's test). In addition, DVL significantly reduced carrageenan-induced leukocyte migration in the TMJ periarticular tissues mediated by down-regulation of ICAM-1 expression. These results suggest a potential anti-inflammatory effect of DVL in inflammatory conditions of TMJ.
Assuntos
Anti-Inflamatórios , Dioclea/química , Molécula 1 de Adesão Intercelular/biossíntese , Leucócitos/metabolismo , Lectinas de Plantas , Transtornos da Articulação Temporomandibular/tratamento farmacológico , Articulação Temporomandibular/metabolismo , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Movimento Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Leucócitos/patologia , Masculino , Simulação de Acoplamento Molecular , Lectinas de Plantas/química , Lectinas de Plantas/farmacologia , Ratos , Ratos Wistar , Articulação Temporomandibular/patologia , Transtornos da Articulação Temporomandibular/induzido quimicamente , Transtornos da Articulação Temporomandibular/metabolismo , Transtornos da Articulação Temporomandibular/patologiaRESUMO
OBJECTIVE AND DESIGN: To investigate the role of heme oxygenase-1 (HO-1), carbon monoxide (CO), and biliverdin (BVD) in the zymosan-induced TMJ arthritis in rats. MATERIALS AND METHODS: Mechanical threshold was assessed before and 4 h after TMJ arthritis induction in rats. Cell influx, myeloperoxidase activity, and histological changes were measured in the TMJ lavages and tissues. Trigeminal ganglion and periarticular tissues were used for HO-1, TNF-α, and IL-1ß mRNA time course expression and immunohistochemical analyses. Hemin (0.1, 0.3, or 1 mg kg-1), DMDC (0.025, 0.25, or 2.5 µmol kg-1), biliverdin (1, 3, or 10 mg kg-1), or ZnPP-IX (1, 3 or 9 mg kg-1) were injected (s.c.) 60 min before zymosan. ODQ (12.5 µmol kg-1; s.c.) or glibenclamide (10 mg kg-1; i.p.) was administered 1 h and 30 min prior to DMDC (2.5 µmol kg-1; s.c), respectively. RESULTS: Hemin (1 mg kg-1), DMDC (2.5 µmol kg-1), and BVD (10 mg kg-1) reduced hypernociception and leukocyte migration, which ZnPP (3 mg kg-1) enhanced. The effects of DMDC were counteracted by ODQ and glibenclamide. The HO-1, TNF-α, and IL-1ß mRNA expression and immunolabelling increased. CONCLUSIONS: HO-1/BVD/CO pathway activation provides anti-nociceptive and anti-inflammatory effects on the zymosan-induced TMJ hypernociception in rats.
Assuntos
Biliverdina/fisiologia , Monóxido de Carbono/fisiologia , GMP Cíclico , Heme Oxigenase-1/fisiologia , Canais KATP , Nociceptividade/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Artrite/induzido quimicamente , Biliverdina/genética , Citocinas/metabolismo , Regulação para Baixo/efeitos dos fármacos , Heme Oxigenase-1/genética , Masculino , Limiar da Dor , Peroxidase/metabolismo , Bloqueadores dos Canais de Potássio/farmacologia , Ratos , Ratos Wistar , Transtornos da Articulação Temporomandibular/induzido quimicamente , Transtornos da Articulação Temporomandibular/patologia , Gânglio Trigeminal/efeitos dos fármacos , ZimosanRESUMO
Temporomandibular joint (TMJ) disorders are a group of conditions that result in TMJ pain, which frequently limits basic daily activities. Experimental models that allow the study of the mechanisms underlying these inflammatory and pain conditions are of great clinical relevance. The aim of this study was to evaluate nociception, inflammation and participation of the macrophage/microglia cells in the arthritis of the TMJ induced by two phlogistic agents. 84 rats were divided into 2 groups: Zy, which received zymosan intra-articularly, or Cg, which received carrageenan intra-articularly. Mechanical nociception, total leukocyte influx to the synovial fluid and histopathological analyses were evaluated in the TMJ. The participation of macrophage/microglia located in trigeminal ganglia (TG) and in the subnucleus caudalis (V-SnC) was assessed immunohistochemically. Both agents induced mechanical hyperalgesia 6h after the induction, but a more persistent algesic state was perceived in the Cg group, which lasted for 120h. Even though both groups presented increased leukocyte influx, the Zy-group presented a more intense influx. Zymosan recruited resident macrophage in the trigeminal ganglia 24h after the injection. In the V-SnC, the group Cg presented a more prolonged immunolabeling pattern in comparison with the group Zy. It can be concluded that zymosan induced a more intense infiltrate and peripheral nervous changes, while Cg lead to a moderate TMJ inflammation with prominent changes in the V-SnC.
Assuntos
Artrite/fisiopatologia , Hiperalgesia/fisiopatologia , Medição da Dor/métodos , Dor/fisiopatologia , Transtornos da Articulação Temporomandibular/fisiopatologia , Animais , Artrite/induzido quimicamente , Artrite/diagnóstico , Artrite/patologia , Carragenina/farmacologia , Modelos Animais de Doenças , Hiperalgesia/induzido quimicamente , Hiperalgesia/patologia , Injeções Intra-Articulares , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Masculino , Microglia/efeitos dos fármacos , Microglia/patologia , Nociceptividade/efeitos dos fármacos , Nociceptividade/fisiologia , Dor/induzido quimicamente , Dor/patologia , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Transtornos da Articulação Temporomandibular/induzido quimicamente , Transtornos da Articulação Temporomandibular/patologia , Gânglio Trigeminal/citologia , Gânglio Trigeminal/efeitos dos fármacos , Zimosan/farmacologiaRESUMO
BACKGROUND: We investigated both the efficacy and the sub-chronic toxicity of Tephrosia toxicariaâ Pers. in the zymosan-induced temporomandibular joint (TMJ) inflammatory hypernociception in rats evaluating the possible role of heme oxygenase-1 (HO-1). METHODS: Rats were pretreated with T. toxicaria (0.2, 2.0 or 20 mg/kg) 60 min before the intra-articular injection of zymosan (2 mg, 40 µL) in the left TMJ. In another series of experiments, rats were treated with ZnPP-IX (3 mg/kg), a specific HO-1 inhibitor, before T. toxicaria (20 mg/kg). Von Frey test was used to evaluate inflammatory hypernociception (g) 4 h after zymosan injection. Six hours after zymosan injection, the synovial lavage was collected for total cell count and myeloperoxidase (MPO) activity, and joint tissue for histopathological analysis and immunohistochemistry for HO-1. To evaluate the sub-chronic toxicity, mice received T. toxicaria (20 mg/kg) or saline once a day for 14 days to analyse body mass, organ weight and biochemical parameters. RESULTS: T. toxicaria partially reversed the zymosan-induced head withdrawal threshold, the number of cells and the MPO activity. T. toxicaria reduced the inflammatory cell influx in the synovial membrane. TMJ immunohistochemical analyses treated with T. toxicaria showed increased HO-1 expression. These effects of T. toxicaria were not observed in the presence of ZnPP-IX. T. toxicaria treatment for 14 days did not show significant signs of toxicity when administrated to mice. CONCLUSIONS: T. toxicaria did not produce any signs of toxicity and effectively decreased zymosan-induced TMJ inflammatory hypernociception dependent, at least in part, upon the HO-1 pathway integrity.
Assuntos
Heme Oxigenase-1/metabolismo , Hiperalgesia/tratamento farmacológico , Fitoterapia , Preparações de Plantas/farmacologia , Transtornos da Articulação Temporomandibular/tratamento farmacológico , Tephrosia , Animais , Modelos Animais de Doenças , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/farmacologia , Heme Oxigenase-1/antagonistas & inibidores , Hiperalgesia/induzido quimicamente , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Masculino , Redes e Vias Metabólicas , Camundongos , Preparações de Plantas/administração & dosagem , Preparações de Plantas/efeitos adversos , Protoporfirinas/administração & dosagem , Protoporfirinas/farmacologia , Ratos , Ratos Wistar , Transtornos da Articulação Temporomandibular/induzido quimicamente , Transtornos da Articulação Temporomandibular/fisiopatologia , Zimosan/farmacologiaRESUMO
Temporomandibular disorder (TMD) is prevalent in dental clinics and can involve problems with the masticatory muscles or the temporomandibular joints (TMJ). The pain of TMD is frequently associated with inflammation in the TMJs, but it's etiology is considered to be multifactorial and includes biologic, behavioral, environmental, social, emotional and cognitive factors. The purpose of this investigation was to evaluate the anxiety-like behavior in rats exposed to temporomandibular inflammation via injection of Freund's Adjuvant (CFA) with the elevated plus maze (EPM) and light/dark box (LDB) tests and to evaluate nociceptive behavior with the von Frey test at different periods. Moreover, this study measured TMJ inflammation using plasma extravasation (Evans blue test) and the intraarticular infiltration of polymorphonuclear neutrophils (myeloperoxidase quantification). The results showed that rats that were submitted to TMJ inflammation exhibited a decreased number of entries into the open arms of the EPM and a decrease in the time spent in the light compartment and in the number of transitions in the LDB. Additionally, the number of entries in closed arms in the EPM, used as indicator of locomotor activity, did not alter between treatments. Furthermore, increases in mechanical sensitivity and increases in plasma extravasation in the joint tissue occurred throughout the inflammation process, along with an increase in myeloperoxidase in the synovial fluid of TMJ. Our results suggest that the temporomandibular inflammation induced by CFA produced anxiety-like behaviors in rats and induced nociceptive behavior across different periods of inflammation.
Assuntos
Ansiedade/psicologia , Inflamação/patologia , Inflamação/psicologia , Dor Nociceptiva/patologia , Dor Nociceptiva/psicologia , Transtornos da Articulação Temporomandibular/patologia , Transtornos da Articulação Temporomandibular/psicologia , Animais , Ansiedade/complicações , Comportamento Animal , Extravasamento de Materiais Terapêuticos e Diagnósticos/patologia , Adjuvante de Freund , Inflamação/induzido quimicamente , Inflamação/complicações , Masculino , Infiltração de Neutrófilos , Dor Nociceptiva/induzido quimicamente , Dor Nociceptiva/complicações , Peroxidase/metabolismo , Ratos , Líquido Sinovial/metabolismo , Transtornos da Articulação Temporomandibular/induzido quimicamente , Transtornos da Articulação Temporomandibular/complicações , Fatores de TempoRESUMO
Temporomandibular joint (TMJ) arthritis is a common cause of orofacial pain. In the present study, the modulatory effects of N-methyl-d-aspartate receptors (NMDA-Rs) and magnesium were investigated in TMJ arthritis hypernociception. Male Wistar rats received an intra-articular injection of carrageenan (Cg) in the TMJ, and mechanical hypernociception was measured. The NMDA-R antagonist, MK-801, and magnesium chloride (MgCl2 ) were administered before arthritis induction. Magnesium deficiency was promoted by feeding rats a synthetic magnesium-free diet for 9 d before injection of Cg. The Cg induced mechanical hypernociception that lasted for 120 h. MK-801 inhibited this hypernociceptive state. MgCl2 pretreatment prevented Cg-induced hypernociception and altered the nociceptive threshold in the absence of Cg. Magnesium deficiency increased hypernociception and induced spontaneous hypernociceptive behavior. TMJ arthritis increased the expression of mRNA for all NMDA-R subunits and immunostaining of phosphorylated NR1 (phospho-NR1). MgCl2 inhibited expression of NR2B mRNA and phospho-NR1 immunostaining and increased expression of NR3 mRNA. Magnesium deficiency increased expression of both NR1 and NR3 mRNAs and phospho-NR1 immunostaining in the trigeminal subnucleus caudalis. We found that magnesium modulates nociceptive behavior and induces NMDA-R subunit rearrangement in the subnucleus caudalis. The present results may lead to a better understanding of central processing in the nociceptive trigeminal pathway and the development of new approaches to treat orofacial pain with a TMJ origin.
Assuntos
Deficiência de Magnésio/metabolismo , Magnésio/farmacologia , Osteoartrite/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Transtornos da Articulação Temporomandibular/metabolismo , Núcleo Inferior Caudal do Nervo Trigêmeo/metabolismo , Nervo Trigêmeo/efeitos dos fármacos , Análise de Variância , Animais , Carragenina , Expressão Gênica , Magnésio/sangue , Deficiência de Magnésio/induzido quimicamente , Masculino , Dados de Sequência Molecular , Dor Nociceptiva/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transtornos da Articulação Temporomandibular/induzido quimicamente , Transtornos da Articulação Temporomandibular/tratamento farmacológico , Fatores de Tempo , Nervo Trigêmeo/metabolismoRESUMO
The 5-hydroxytryptamine (serotonin, 5-HT) is an important inflammatory mediator found in high levels in the synovial fluid of the temporomandibular joint (TMJ) of patients with inflammatory pain. In this study, we used the nociceptive behavior responses, measured as flinching the head and rubbing the orofacial region, as a nociceptive assay. We demonstrated that the local blockade of the 5-HT3 receptor and ß1 or ß2-adrenoceptors, the depletion of norepinephrine in the sympathetic terminals and the local inhibition of cyclooxygenase significantly reduced 5-HT-induced TMJ nociception. These results demonstrated that 5-HT induces nociception in the TMJ region by the activation of ß1 and ß2 adrenoceptors located in the TMJ region and local release of sympathetic amines and prostaglandins. Therefore, the high levels of 5-HT in the synovial fluid of patients with TMJ inflammatory pain may contribute to TMJ pain by similar mechanisms.
Assuntos
Agonistas Adrenérgicos beta , Dor Facial/induzido quimicamente , Mediadores da Inflamação/metabolismo , Nociceptores/efeitos dos fármacos , Serotonina/farmacologia , Transtornos da Articulação Temporomandibular/induzido quimicamente , Antagonistas Adrenérgicos beta/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Atenolol/farmacologia , Movimento Celular/efeitos dos fármacos , Dor Facial/metabolismo , Indometacina/farmacologia , Injeções , Masculino , Medição da Dor/efeitos dos fármacos , Peroxidase/metabolismo , Polissacarídeos/farmacologia , Ratos , Ratos Wistar , Receptores Adrenérgicos beta/efeitos dos fármacos , Sistema Nervoso Simpático/fisiopatologia , Articulação Temporomandibular , Transtornos da Articulação Temporomandibular/metabolismoRESUMO
AIM: The aim of this study was to evaluate, by light microscopy, the effects of laser phototherapy (LPT) at 780 nm or a combination of 660 and 790 nm, on the inflammatory process of the rat temporomandibular joint (TMJ) induced by carrageen. BACKGROUND: Temporomandibular disorders (TMDs) are frequent in the population and generally present an inflammatory component. Previous studies have evidenced positive effects of laser phototherapy on TMDs. However, its mechanism of action on the inflammation of the TMJ is not known yet. MATERIALS AND METHODS: Eighty-five Wistar rats were divided into 9 groups: G1, Saline; G2, Saline + LPT IR; G3, Saline + LPT IR + R; G4, Carrageenan; G5, Carrageenan + LPT IR; G6, Carrageenan + LPT IR + R; G7, previous LPT + Carrageenan; G8, previous LPT + carrageenan + LPT IR; and G9, previous LPT + carrageenan + LPT IR + R, and then subdivided in subgroups of 3 and 7 days. After animal death, specimens were taken, routinely cut and stained with HE, Sirius Red, and Toluidine Blue. Descriptive analysis of components of the TMJ was done. The synovial cell layers were counted. RESULTS: Injection of saline did not produced inflammatory reaction and the irradiated groups did not present differences compared to nonirradiated ones. After carrageenan injection, intense inflammatory infiltration and synovial cell layers proliferation were observed. The infrared irradiated group presented less inflammation and less synovial cell layers number compared to other groups. Previous laser irradiation did not improve the results. CONCLUSION: It was concluded that the LPT presented positive effects on inflammatory infiltration reduction and accelerated the inflammation process, mainly with IR laser irradiation. The number of synovial cell layers was reduced on irradiated group.
Assuntos
Terapia com Luz de Baixa Intensidade/métodos , Transtornos da Articulação Temporomandibular/radioterapia , Animais , Carragenina , Inflamação/radioterapia , Lasers Semicondutores/uso terapêutico , Masculino , Fotomicrografia , Ratos , Ratos Wistar , Articulação Temporomandibular/efeitos dos fármacos , Articulação Temporomandibular/efeitos da radiação , Transtornos da Articulação Temporomandibular/induzido quimicamenteRESUMO
Temporomandibular joint pain-related conditions are generally characterized by local inflammation; however, little studies have focused on the role of gonadal hormones in the expression of inflammatory mediators, such as cytokines. Therefore, we asked whether gonadal steroid hormones affect formalin-induced cytokines expression in the rat temporomcandibular joint. The expression of tumor necrosis factor alpha (TNF-α), interleukin (IL)-1ß, and cytokine-induced neutrophil chemoattractant (CINC)-1 was significantly higher in males than in diestrus and proestrus females and was decreased by orchiectomy and restored by testosterone replacement. The expression of IL-6 was significantly higher in diestrus and proestrus females than in males, and was decreased by ovariectomy and restored by estradiol or progesterone administration. We conclude that testosterone increases the expression of TNF-α, IL-1ß and CINC-1, and estradiol and progesterone increase the expression of IL-6. New clinical approaches based on inhibition of pro-inflammatory mediators are starting to supplant traditional immunosuppressive therapies and gonadal hormones may influence their effectiveness or clinical dosage.
Assuntos
Citocinas/metabolismo , Hormônios Esteroides Gonadais/metabolismo , Articulação Temporomandibular/metabolismo , Animais , Quimiocina CXCL1/metabolismo , Estradiol/farmacologia , Feminino , Mediadores da Inflamação/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , Orquiectomia , Ovariectomia , Medição da Dor , Progesterona/farmacologia , Ratos , Caracteres Sexuais , Articulação Temporomandibular/efeitos dos fármacos , Transtornos da Articulação Temporomandibular/induzido quimicamente , Transtornos da Articulação Temporomandibular/metabolismo , Testosterona/farmacologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The temporomandibular joint (TMJ) formalin test was used to evaluate the effects of acute restraint stress on the nociceptive behavioral responses of female rats during proestrus and estrus phases of the estrous cycle. Rats were subjected to one session of restraint stress (15, 30 min or 1 h). They were then either immediately killed to allow the collection of blood for hormonal radioimmunoassay determinations or subjected to TMJ formalin test to evaluate nociception. All stress protocols significantly raised the plasma concentrations of corticosterone. The performance of rats subjected to 15 and 30 min of restraint stress was similar to that of control rats, whereas rats that were stressed for 1 h showed a decrease in nociceptive responses, during both proestrus and estrus phases. The stress-induced analgesia (SIA) was greater in the proestrus phase. To evaluate the role of kappa-opioid receptors, the selective receptor kappa-opioid antagonist nor-binaltorphimine (nor-BNI; 200 microg or saline) was injected into the TMJ 24 h prior to the 1 h stress period and the TMJ formalin test. The local administration of nor-BNI partially reversed the SIA during the proestrus phase. These findings suggest that (1) acute stress for 1 h can produce analgesia both during proestrus and estrus phases; this effect is greater during the proestrus phase and (2) kappa-opioid receptor activation is involved in the SIA observed in the proestrus phase.
Assuntos
Nociceptores/fisiologia , Medição da Dor , Dor/fisiopatologia , Estresse Fisiológico/fisiologia , Transtornos da Articulação Temporomandibular/fisiopatologia , Doença Aguda , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Estro/fisiologia , Feminino , Formaldeído/farmacologia , Naltrexona/análogos & derivados , Naltrexona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Nociceptores/efeitos dos fármacos , Dor/induzido quimicamente , Proestro/fisiologia , Ratos , Ratos Wistar , Receptores Opioides/fisiologia , Restrição Física , Articulação Temporomandibular/efeitos dos fármacos , Articulação Temporomandibular/fisiologia , Transtornos da Articulação Temporomandibular/induzido quimicamenteRESUMO
BACKGROUND AND OBJECTIVES: Stimulations with formalin in the orofacial region can be related to transient or subacute nociceptive activity and behavioral changes. The evaluation of behavioral changes induced by persistent or chronic irritating nociceptive substance has not yet been described.METHOD: Complete Freund's Adjuvant (CFA) was injected in the temporomandibular joint (TMJ) region of rats and analyzed comparing it to the groups treated with saline and 2.5% formalin. In addition, behaviors such as grooming, freezing, rest/sleeping and chewing-like were electronically observed and quantified.RESULTS: It was shown that the chewing-like behavior was significantly increased and that it was inhibited by indometacin (5 mg/kg) and morphine (4 mg/kg). CONCLUSION: These results suggest that chewing-like may be a possible behavior of persistent or chronic orofacial pain, and may be a tool for clinical-pharmacological studies.
JUSTIFICATIVA E OBJETIVOS: Estímulos com formalina na região orofacial podem estar relacionados com a atividade nociceptiva e as alterações comportamentais transitórias ou subagudas. A avaliação de comportamentos sob ação de substância irritante nociceptiva persistente e crônica ainda não foi descrita.MÉTODO: Foi feita injeção de adjuvante completo de Freund (ACF) na região da articulação temporomandibular (ATM) de ratos e foi analisada comparando-a com os grupos tratados com salina e formalina a 2,5%. Além disso, foram observados e quantificados eletronicamente os comportamentos grooming, freezing, rest/sleeping e chewing-like (mastigação). RESULTADOS: Observou-se que o comportamento mastigação (chewing-like) estava significativamente aumentado e que ele foi inibido pela indometacina (5 mg/kg) e morfina (4 mg/kg).CONCLUSÃO: Esses resultados sugerem ser o chewing-like um possível comportamento de dor orofacial persistente, oferecendo-se como instrumento para análise clínico-farmacológica
Assuntos
Animais , Masculino , Ratos , Analgésicos/farmacologia , Dor Facial/fisiopatologia , Mastigação/efeitos dos fármacos , Transtornos da Articulação Temporomandibular/fisiopatologia , Analgésicos Opioides/uso terapêutico , Anestésicos Locais/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Comportamento Animal , Modelos Animais de Doenças , Adjuvante de Freund , Indometacina/uso terapêutico , Lidocaína/uso terapêutico , Morfina/uso terapêutico , Ratos Wistar , Transtornos da Articulação Temporomandibular/induzido quimicamenteRESUMO
In order to investigate a putative role for nitric oxide (NO) in the central nociceptive processing following carrageenan-induced arthritis in the rat temporomandibular joint (TMJ), we analyzed the immunoreactivity, gene expression and activity of nitric oxide synthases (NOS) in the caudal part of the spinal trigeminal nucleus (Sp5C) during the acute (24 h), chronic (15 days) and chronic-active (14 days-24 h) arthritis. In addition, evaluation of head-withdrawal threshold was carried out in all phases of arthritis under chronic inhibition of nNOS with the selective inhibitor 7-nitroindazole (7-NI). Neurons with nNOS-like immunoreactivity (nNOS-LI) were concentrated mainly in the lamina II of the Sp5C, showing no significant statistical difference during arthritis. Only a discrete percentage of nNOS-LI neurons expressed Fos immunoreactivity. The mRNA expression for both nNOS and endothelial nitric oxide synthases (eNOS) presented no noticeable differences among the groups. No expression of inducible nitric oxide synthase (iNOS) was detected in the Sp5C by either immunohistochemistry or reverse-transcription polymerase chain reaction (RT-PCR). Ca(2+)-dependent NOS activity in the ipsilateral Sp5C was significantly higher (108.3+/-49.2%; P<0.01) in animals during the chronic arthritis. Interestingly, this increased activity was completely abolished 24 h later, in the chronic-active arthritis. Finally, head-withdrawal threshold decreased significantly in the chronic arthritis in animals under 7-NI chronic inhibition. In conclusion, nNOS immunoreactivity and mRNA expression are stable in the Sp5C during TMJ arthritis evolution, but its activity significantly increases in the chronic-phases supporting an antinociceptive role of the nNOS as evidenced by pain threshold experiment.
Assuntos
Artralgia/metabolismo , Artrite Experimental/metabolismo , Óxido Nítrico Sintase Tipo I/metabolismo , Óxido Nítrico/metabolismo , Transtornos da Articulação Temporomandibular/metabolismo , Núcleo Inferior Caudal do Nervo Trigêmeo/metabolismo , Animais , Artralgia/induzido quimicamente , Artralgia/fisiopatologia , Artrite Experimental/induzido quimicamente , Artrite Experimental/fisiopatologia , Carragenina/farmacologia , Doença Crônica , Modelos Animais de Doenças , Inibidores Enzimáticos/farmacologia , Indazóis/farmacologia , Mediadores da Inflamação/farmacologia , Masculino , Óxido Nítrico Sintase Tipo I/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Nociceptores/metabolismo , Medição da Dor , Limiar da Dor/fisiologia , Células do Corno Posterior/metabolismo , Células do Corno Posterior/fisiopatologia , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Transtornos da Articulação Temporomandibular/induzido quimicamente , Transtornos da Articulação Temporomandibular/fisiopatologia , Núcleo Inferior Caudal do Nervo Trigêmeo/fisiopatologiaRESUMO
Temporomandibular disorders represent one of the major challenges in dentistry therapeutics. This study was undertaken to evaluate the time course of carrageenan-induced inflammation in the rat temporomandibular joint (TMJ) and to investigate the role of tachykinin NK(1) receptors. Inflammation was induced by a single intra-articular (i.art.) injection of carrageenan into the left TMJ (control group received sterile saline). Inflammatory parameters such as plasma extravasation, leukocyte influx and mechanical allodynia (measured as the head-withdrawal force threshold) and TNFalpha and IL-1beta concentrations were measured in the TMJ lavages at selected time-points. The carrageenan-induced responses were also evaluated after treatment with the NK(1) receptor antagonist SR140333. The i.art. injection of carrageenan into the TMJ caused a time-dependent plasma extravasation associated with mechanical allodynia, and a marked neutrophil accumulation between 4 and 24h. Treatment with SR140333 substantially inhibited the increase in plasma extravasation and leukocyte influx at 4 and 24h, as well as the production of TNFalpha and IL-1beta into the joint cavity, but failed to affect changes in head-withdrawal threshold. The results obtained from the present TMJ-arthritis model provide, for the first time, information regarding the time course of this experimental inflammatory process. In addition, our data show that peripheral NK(1) receptors mediate the production of both TNFalpha and IL-1beta in the TMJ as well as some of the inflammatory signs, such as plasma extravasation and leukocyte influx, but not the nociceptive component.
Assuntos
Inflamação/patologia , Receptores da Neurocinina-1/fisiologia , Transtornos da Articulação Temporomandibular/patologia , Animais , Carragenina , Interpretação Estatística de Dados , Extravasamento de Materiais Terapêuticos e Diagnósticos , Inflamação/induzido quimicamente , Interleucina-1beta/metabolismo , Contagem de Leucócitos , Masculino , Antagonistas dos Receptores de Neurocinina-1 , Dor/etiologia , Dor/fisiopatologia , Peroxidase/metabolismo , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Quinuclidinas/farmacologia , Quinuclidinas/uso terapêutico , Compostos Radiofarmacêuticos , Ratos , Ratos Wistar , Soroalbumina Radioiodada , Substância P/metabolismo , Transtornos da Articulação Temporomandibular/induzido quimicamente , Fator de Necrose Tumoral alfa/metabolismoRESUMO
UNLABELLED: The aim of this study was to investigate the influence of sex and ovarian hormones on formalin- and glutamate-induced temporomandibular joint (TMJ) nociception in rats. The influence of sex and ovarian hormones on the nociceptive behavior induced by formalin or glutamate was virtually the same. The nociceptive behavior of males was similar to that of females in the proestrus phase of the estrous cycle but was significantly lower than that in the diestrus phase. Since the serum level of estradiol but not of progesterone was significantly higher in the proestrus than in the diestrus phase, these data suggest that females with lower endogenous serum level of estradiol have an exacerbation of TMJ nociception. The nociceptive behavior of ovariectomized rats was similar to that of diestrus females and significantly greater than that of proestrus females. Although the administration of estradiol or progesterone in ovariectomized females significantly reduced TMJ nociception, the combination of both hormones did not increase the antinociceptive effect induced by each of them. These findings suggest that estradiol and progesterone decrease TMJ nociception in an independent way. PERSPECTIVE: We report that ovarian hormones have an antinociceptive effect on the TMJ formalin and glutamate nociceptive behavior models. Therefore, the greater prevalence and severity of TMJ pain in women of reproductive age may be a consequence of hormonal fluctuation during the reproductive cycle, in that during low endogenous estradiol serum level TMJ pain sensitivity is increased, enhancing the risk of females experiencing TMJ pain.
Assuntos
Estradiol/fisiologia , Nociceptores/fisiologia , Dor/fisiopatologia , Progesterona/fisiologia , Transtornos da Articulação Temporomandibular/fisiopatologia , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Diestro/fisiologia , Estradiol/sangue , Feminino , Formaldeído/administração & dosagem , Formaldeído/toxicidade , Ácido Glutâmico/administração & dosagem , Ácido Glutâmico/toxicidade , Humanos , Injeções Intra-Articulares , Injeções Intraperitoneais , Masculino , Nociceptores/efeitos dos fármacos , Ovariectomia , Dor/induzido quimicamente , Medição da Dor/métodos , Proestro/fisiologia , Progesterona/sangue , Radioimunoensaio , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Fatores Sexuais , Articulação Temporomandibular/efeitos dos fármacos , Articulação Temporomandibular/fisiopatologia , Transtornos da Articulação Temporomandibular/sangue , Transtornos da Articulação Temporomandibular/induzido quimicamenteRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Cocoa bean preparations were first used by the ancient Maya and Aztec civilizations of South America to treat a variety of medical ailments involving the cardiovascular, gastrointestinal, and nervous systems. Diets rich in foods containing abundant polyphenols, as found in cocoa, underlie the protective effects reported in chronic inflammatory diseases. Release of calcitonin gene-related peptide (CGRP) from trigeminal nerves promotes inflammation in peripheral tissues and nociception. AIM OF THE STUDY: To determine whether a methanol extract of Theobroma cacao L. (Sterculiaceae) beans enriched for polyphenols could inhibit CGRP expression, both an in vitro and an in vivo approach was taken. RESULTS: Treatment of rat trigeminal ganglia cultures with depolarizing stimuli caused a significant increase in CGRP release that was repressed by pretreatment with Theobroma cacao extract. Pretreatment with Theobroma cacao was also shown to block the KCl- and capsaicin-stimulated increases in intracellular calcium. Next, the effects of Theobroma cacao on CGRP levels were determined using an in vivo model of temporomandibular joint (TMJ) inflammation. Capsaicin injection into the TMJ capsule caused an ipsilateral decrease in CGRP levels. Theobroma cacao extract injected into the TMJ capsule 24h prior to capsaicin treatment repressed the stimulatory effects of capsaicin. CONCLUSIONS: Our results demonstrate that Theobroma cacao extract can repress stimulated CGRP release by a mechanism that likely involves blockage of calcium channel activity. Furthermore, our findings suggest that the beneficial effects of diets rich in cocoa may include suppression of sensory trigeminal nerve activation.
Assuntos
Cacau/química , Peptídeo Relacionado com Gene de Calcitonina/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Extratos Vegetais/farmacologia , Transtornos da Articulação Temporomandibular/tratamento farmacológico , Animais , Animais Recém-Nascidos , Peptídeo Relacionado com Gene de Calcitonina/genética , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Capsaicina , Modelos Animais de Doenças , Feminino , Flavonoides/química , Flavonoides/farmacologia , Humanos , Indígenas Sul-Americanos , Medicina Tradicional , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fenóis/química , Fenóis/farmacologia , Polifenóis , Ratos , Ratos Sprague-Dawley , Sementes , América do Sul , Transtornos da Articulação Temporomandibular/induzido quimicamente , Gânglio Trigeminal/efeitos dos fármacos , Gânglio Trigeminal/metabolismoRESUMO
A considerable amount of evidence suggests that temporomandibular joint (TMJ) pain associated with temporomandibular disorder results, at least in part, from an inflammatory episode. Although histamine can cause pain, it is not clear whether this mediator induces nociception in the TMJ. In this study, we investigated the contribution of endogenous histamine to formalin-induced nociception in the TMJ of rats. We also investigated whether the administration of histamine induces nociception in the TMJ and, if so, whether this effect is mediated by an indirect action on primary afferent nociceptors. Local administration of the H1-receptor antagonist pyrilamine prevented formalin-induced nociception in the TMJ in a dose-dependent manner. Local administration of histamine (250 microg) in the TMJ induced nociceptive behavior that was inhibited by co-administration of the lidocaine N-ethyl bromide quaternary salt QX-314 (2%) or the selective H1-receptor antagonist pyrilamine (400 microg). Nociception induced by histamine was also inhibited by pre-treatment with sodium cromoglycate (800 microg) and by co-administration of the 5-HT(3) receptor antagonist tropisetron (400 mug), while pyrilamine (400 mug) did not inhibit nociception induced by 5-hydroxytryptamine (5-HT, 250 microg) in the TMJ. Furthermore, histamine, in a dose that did not induce nociception by itself, strongly enhanced 5-HT-induced nociception. Finally, the administration of a sub-threshold dose of 5-HT (100 microg), but not of histamine (100 microg), elicited nociception in the TMJ previously challenged with the inflammatory agent carrageenan (100 microg). In conclusion, these data suggest that histamine induces TMJ nociception by an indirect mechanism involving endogenous release of 5-HT and activation of 5-HT(3) receptors on sensory afferents. It is proposed that histamine activates the H1 receptor to induce the release of 5-HT which depolarizes the nociceptor by activating 5-HT(3) receptor.
Assuntos
Histamina/farmacologia , Dor , Receptores Histamínicos H1/metabolismo , Transtornos da Articulação Temporomandibular , Articulação Temporomandibular , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Comportamento Animal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Interações Medicamentosas , Histamina/metabolismo , Antagonistas dos Receptores Histamínicos H1/farmacologia , Masculino , Dor/induzido quimicamente , Dor/tratamento farmacológico , Dor/metabolismo , Dor/fisiopatologia , Medição da Dor , Ratos , Ratos Wistar , Serotonina/metabolismo , Serotonina/farmacologia , Serotonina/fisiologia , Antagonistas da Serotonina/farmacologia , Articulação Temporomandibular/efeitos dos fármacos , Articulação Temporomandibular/metabolismo , Transtornos da Articulação Temporomandibular/induzido quimicamente , Transtornos da Articulação Temporomandibular/tratamento farmacológico , Transtornos da Articulação Temporomandibular/metabolismo , Transtornos da Articulação Temporomandibular/fisiopatologiaRESUMO
UNLABELLED: The lower prevalence of many pain conditions, including temporomandibular dysfunctions, in men than in women has not as yet been clarified. The aim of this study was to investigate the effect of testosterone on the risk of development of temporomandibular joint (TMJ) pain and on acute persistent TMJ pain. The TMJ formalin test was used as an experimental assay in the rat. Intra-TMJ 0.5% formalin induced a significant nociceptive behavior in naive female rats and gonadectomized male rats but not in naive male rats, suggesting that naive male rats have a lower risk for development of TMJ pain. The finding that the serum level of testosterone but not of estrogen and progesterone significantly decreased in gonadectomized male rats suggests that testosterone is the hormone underlying the decreased naive male rat's risk for development of TMJ pain. The magnitude of the nociceptive behaviors induced by intra-TMJ 1.5% formalin was similar in gonadectomized and naive male rats. Therefore, in contrast to the protective role of testosterone in TMJ pain development, testosterone, at physiological serum levels, does not appear to modulate acute persistent TMJ pain induced by the TMJ injection of 1.5% formalin. At a supraphysiological serum level, however, testosterone significantly attenuated 1.5% formalin-induced nociception in male rats but not in female rats. This antinociceptive effect was not mediated by estrogen derived from testosterone aromatization, because estrogen administration did not affect 1.5% formalin-induced TMJ nociception in gonadectomized male rats. PERSPECTIVE: The present findings not only help to explain the lower prevalence of TMJ pain in males versus females but also show that testosterone reduces TMJ pain at supraphysiological serum levels.